title: Addition of 2-deoxyglucose enhances growth inhibition but reverses acidification in colon cancer cells treated with phenformin.
abstract: A report that effects of butyrate on some cells may be mediated by activation of AMP-activated protein kinase (AMPK) prompted this study which examines if other AMPK activators can induce differentiation and inhibit proliferation of colon cancer cells in a manner similar to butyrate. Using induction of alkaline phosphatase as a marker, it was observed that compound C, an AMPK inhibitor, is able to reduce the differentiating effect of butyrate on SW1116 and Caco-2 colon cancer cells. Metformin was observed to be less effective than butyrate in the induction of alkaline phosphatase but was more effective as a growth inhibitor. Phenformin was found to be a more potent growth inhibitor than metformin and both compounds cause acidification of the medium when incubated with colon cancer cells. Combined incubation of 2-deoxyglucose with either of the biguanides prevented the acidification of the medium but enhanced the growth inhibitory effects.
authors.affiliation: Department of Biochemistry and Molecular Biology, UMDNJ - New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA. lea@umdnj.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Lea
authors.forename: Jerel
authors.initials: J
authors.lastname: Chacko
authors.forename: Sandhya
authors.initials: S
authors.lastname: Bolikal
authors.forename: Ji Y
authors.initials: JY
authors.lastname: Hong
authors.forename: Ryan
authors.initials: R
authors.lastname: Chung
authors.forename: Andres
authors.initials: A
authors.lastname: Ortega
authors.forename: Charles
authors.initials: C
authors.lastname: desbordes
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000096:biosynthesis / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology; D018938:Caco-2 Cells; D048708:Cell Growth Processes / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D003847:Deoxyglucose / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010629:Phenformin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D002087:Butyrates; D003847:Deoxyglucose; D010629:Phenformin; D000263:Adenylate Kinase; D000469:Alkaline Phosphatase